title: Experiences in fragment-based lead discovery.
abstract: This chapter summarizes the experience at Vernalis over the past decade in developing and applying fragment-based discovery methods across a range of different targets. The emphasis will be on the practical aspects of the different biophysical techniques (surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), isothermal titration calorimetry, nuclear magnetic resonance, and X-ray crystallography) that can be used to identify fragments that bind to targets and a discussion of the criteria and strategies for selecting and evolving fragments to lead compounds.
authors.affiliation: Vernalis (R&D) Ltd., Granta Park, Cambridge, United Kingdom; YSBL & HYMS, University of York, Heslington, York, United Kingdom.
authors.forename: Roderick E
authors.initials: RE
authors.lastname: Hubbard
authors.forename: James B
authors.initials: JB
authors.lastname: Murray
mesh_terms: D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005470:Fluorometry / Q000379:methods; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006860:Hydrogen Bonding; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011485:Protein Binding; D011487:Protein Conformation; D012118:Resorcinols / Q000737:chemistry / Q000494:pharmacology; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance / Q000379:methods
chemical_list: D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D012118:Resorcinols; D054852:Small Molecule Libraries